Novel GLP-1/GLP-2 Agent Reduces Body Weight by Up to 8.3% in Phase 1b Obesity Trial
ADA 2025: Dapiglutide showed promising safety and weight loss results in a phase 1b trial, targeting obesity and inflammation with once-weekly dosing.
Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist in development for chronic weight management, demonstrated favorable safety and tolerability with dose-dependent weight reduction in a 13-week phase 1b clinical trial.
The findings were presented at the American Diabetes Association’s (ADA) 85th Scientific Sessions, June 20-23, 2025, in Chicago, IL.
“Dapiglutide is a first-in-class GLP-1R/GLP-2R agonist in development for weight management designed to address low-grade inflammation and obesity-associated co-morbidities,” presenting author Tim Heise, MD, cofounder, lead scientist, and chairman of the board of directors at Profil, a contract research organization based in Neuss, Germany, and colleagues wrote in the study abstract.
The results are from part 1 of the multiple ascending dose study, whose main purpose was to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of dapiglutide.
The double-blind, placebo-controlled study enrolled 54 adults with a body mass index (BMI) between 27.0 and 39.9 kg/m² but no diabetes. Approximately 85% of participants were men, with a median age of 46 years, a median BMI of 30.0 kg/m², and median baseline weight of 95.1 kg. Participants were randomized (14:4) across 3 escalating-dose cohorts to receive once-weekly subcutaneous injections of dapiglutide targeting final doses of 7.5 mg, 10 mg, and 13 mg, or placebo. Dose escalation occurred every 2 weeks during the 13-week treatment period. The follow-up period for safety outcomes lasted through 19 weeks. No lifestyle interventions were included, researchers noted in the abstract.
Dapiglutide was well tolerated, with no treatment-related serious or severe adverse events reported. The most common adverse events were gastrointestinal (GI) disorders (41.7% of the placebo group, 71.4% of the dapiglutide 7.5 mg group, 85.7% of the dapiglutide 10 mg group and 85.7% of the dapiglutide 13 mg group) and respiratory, thoracic, and mediastinal disorders (33.3% of the placebo group, 57.1% of the dapiglutide 7.5 mg group, 28.6% of the dapiglutide 10 mg group and 35.7% of the dapiglutide 13 mg group), Heise said during a presentation.
Decreased appetite occurred in 21.4% of the dapiglutide 7.5 mg group, 71.4% of the dapiglutide 10 mg group and 7.1% of the dapiglutide 13 mg group, which could be a sign of efficacy, Heise added during the presentation. Most events were mild in severity. Two participants in the dapiglutide group discontinued treatment due to GI-related adverse events, according to the study abstract.
Pharmacokinetic data showed linear dose proportionality with a mean half-life of 112 to 119 hours across dose levels, supporting once-weekly administration. Anti-drug antibodies (ADA) were detected at low titers in 14.3% of participants receiving dapiglutide, but these did not appear to impact efficacy, pharmacokinetics, or safety.
By week 13, participants had received their target dose for 5 to 9 weeks depending on the cohort. The estimated placebo-corrected mean weight reductions were 6.7% for the 7.5 mg group, 8.3% for the 10 mg group, and 7.1% for the 13 mg group. Participants in the placebo arm gained a mean of 2.1% in body weight over the study period, according to investigators.
The results indicate that dapiglutide has a safety and efficacy profile consistent with other incretin therapies, while offering potential additional benefits through GLP-2 receptor activity, such as addressing obesity-related low-grade inflammation. “The half-life of dapiglutide is suitable for once-weekly dosing. Doses up to 26 mg are currently being evaluated,” Heise and colleagues concluded.
Part 2 of the study, which covers dose escalation up to 26 mg at 28 weeks, will be presented at a future medical conference.
Source: Maarbjerg SJ, Heise T, Zachariae R, et al. 141-OR: Safety, tolerability, and clinical effects of dapiglutide, a once-weekly GLP-1R/GLP-2R agonist. Diabetes. 2025;74(Supplement_1):141-OR. doi:10.2337/db25-141-OR
